253 Plagemann, P. G. W., Gregory, K. F. and Wroblewski, F. (1961), Biochem. z; 334, 37. Plummer, D. T. and Wilkinson, J. H. (1961), Biochem, J.• 81, 38P. Richterich, R. and Burger, A. (1963), Enzymol. biol, clin., 3, 65. Rosalki, S. B. and Wilkinson, J. H. (1960), Nature. 188, 110. Wachsmuth, E. D., Pfleiderer, G. and Wieland, T. (1964), Biochem. z.. 340, 80. Withycombe, W. A. and Wilkinson, J. H. (1964), Biochem. J., 93, 11P. Classification and Diagnosis of the Glycogen Storage Diseases J. SPENCER-PEET CHARING CROSS HOSPITAL MEDICAL SCHOOL, WEST LONDON HOSPITAL, LONDON, W.6. The Glycogen Storage Diseases form a group of rare inborn errors of metabolism in which there is an abnormality in the amount and some- times also of the structure, of the glycogen stored in the tissues. Defects in one or other of the enzymes closely concerned with glycogen meta- bolism, have been demonstrated in each type of the disease. It is conventional and convenient to classify the diseases according to the relevant enzyme defect, and each type may also be referred to by a number. The Illingworth (1961) system of numbering will be followed in this paper. Classification of Glycogen Storage Disease. In approximately 95 % of cases the defect is in one of the enzymes on the degradative pathways of glycogen metabolism. The first of the degradative enzymes on the glycogenolytic pathway is phosphorylase. There are at least two distinct forms of this enzyme, one found typically in voluntary muscle, the other in liver. In McArdle's Disease (Type V) the muscle phosphorylase is absent, there is accumulation of glycogen and the inability to use this as a source of energy severely limits muscular exercise. Complete absence of the hepatic form of phosphorylase has not been described, but in some cases in the heterogenous group Type VI, the levels of this enzyme in liver have been found to be considerably reduced. This reduction in hepatic phosphorylase is accompanied by the accumulation of very large amounts of glycogen with a normal structure. Phosphorylase splits 1:4 linked glucosyl units from the terminal branches of the glycogen molecule until 1:6 linked branching points are approached. Further degradation depends on the removal of the 1:6 links by amylo 1:6-glucos- idase thus exposing inner 1:4 linked units to the action of phosphorylase. Deficiency of amylo 1:6-glucosidase leads to accumulation of a phosphorylase limit dextrin in the affected tissue, usually either liver or muscle, or both. (Hers, 1964). Von Gierke's Disease, (Type 1) is associated with the absence of glucose 6-phosphatase and the accumulation of glycogen in the liver and kidneys. Glycogen may be catabolised also in the lyso- somes by a series of enzymes of the amylase type. One of these enzymes, named acid maltase by Hers, is absent in the severe generalised glyco- genosis known as Pompe's Disease (Type II). In this disease, most tissues are affected but the cardiac and voluntary muscles are especially damaged by the accumulation of intralysosomal glycogen. Two rare defects have been described on the pathway of glycogen synthesis. Glycogen syn- thetase, the principal enzyme forming 1:4 linked units of the glycogen molecule, is absent in a disease in which very little glycogen is found in the liver. In Type IV disease the polysaccharide which accumulates resembles the starch com- ponent amylopectin with longer 1:4 linked branches than normal glycogen and relatively fewer 1:6 linked branching points. The enzyme defect in this disease has not been confirmed but is believed to be in the branching enzyme which introduces the 1:6 links. The abnormal glycogen induces a foreign body reaction in the liver and this leads to hepatic failure. (For a review of enzyme defects associated with Glycogen Storage Diseases, see "Control of Glycogen Metabolism" Ciba Foundation Sym- posium. Edited by W. J. Whelan and M. P. Cameron. Churchill. 1964.). Diagnosis of Glycogen Storage Disease. The Glycogenoses may be subdivided into two groups according to the clinical features. In the first group, Types II and V, the presenting symptoms
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